The primary goals of this project are to develop methods to predict structures of membrane proteins from their sequences and available experimental data, to use these methods to develop structural models of specific membrane proteins, and to work with experimental groups to test these models. We have developed a hierarchical approach to modeling membrane proteins. In the first phase we predict which segments cross the membrane and the secondary structure of these segments, in the second phase we predict the relative positions and orientations of the transmembrane segments, and in the third phase we use computer graphics and molecular mechanics energy calculations to produce models that predict positions of all atoms in the regions of the proteins that are modeled. We have developed models through the third phase for members of the following families of proteins: delta lysin, magainins, cecropins, alamethicin, pardaxin, annexins, and voltage-gated potassium channels. Most of our time during the past year was spent developing Phase III models of voltage-gated potassium channels and models of the influenza virus fusion process. We have now established collaborations to begin the fourth phase of modeling of the potassium channel in which energetic factors such as water, lipids, ions, membrane voltages, and entropy are included in the energy calculations and the fifth phase in which functional properties such as gating, ion permeation, and drug binding mechanisms are modeled.